New Treatment Offers Hope for Women With Frequent Hot Flashes

Women plagued by frequent hot flushes during menopause could cut the number of flashes by almost three-quarters, thanks to an exciting new drug compound.

In a trial carried out at Imperial College London, researchers showed that women who suffered seven or more hot flashes a day could reduce the number by as much as 73%, as well as reducing their severity and impact.

The team hopes that this successful early-stage study, involving a drug which targets receptors in the brain, could provide hope for women who are affected by flashes and for whom hormone replacement therapy (HRT) is either unsuitable or not preferred by the patient due to safety concerns.

“If a woman is having more than seven flushes a day and the drug is getting rid of three-quarters of them, that’s pretty life-changing,” said Professor Waljit Dhillo, an NIHR Research Professor from the Department of Medicine. “For day to day living and work, that’s a significant impact on quality of life. If we can reduce flushing by 73% it’s a game-changer for those patients.”

Menopause is when a women’s periods stop and she is no longer able to have children naturally. As the levels of estrogen fall – typically around 45 to 55 years of age – it leads to a number of physical changes, including menopausal flashing and profuse sweating.

For many women, these hot flushes may be little more than an uncomfortable inconvenience. But for some, frequent severe episodes can lead to relentlessly being awoken from sleep with clothes and bed sheets drenched in sweat, which impacts their working, social, and home lives.

HRT can be an effective treatment for some women, but may not be suitable for everyone. The therapy, which involves taking regular estrogen supplements to relieve symptoms, may increase the relative risk of breast cancer or blood clots.

In the latest study, which was funded and led by Professor Dhillo, 28 women with severe flashing were given a new drug compound called MLE4901, originally developed by AstraZeneca and licensed to Millendo Therapeutics, to try to relieve their symptoms.

At the heart of the approach is blocking a chemical called neurokinin B (NKB). In previous studies, analysis of brain tissue from post-menopausal women revealed elevated levels of NKB in their brains. The Imperial team has also previously found that giving NKB to younger women in a temperature-controlled room caused flashing.

Bringing together all of these strands led the researchers to think that blocking the action of the chemical could potentially have the opposite effect and be a new effective treatment for menopausal flashing.

To test the idea, female volunteers with frequent flashing were administered MLE4901 which blocks the NK3 receptors of the brain, where NKB acts, to suppress the action of the chemical.

In a randomized, double-blind, placebo-controlled trial, menopausal women aged between 40 and 62 years old who experienced seven or more hot flashes a day and had not had a period in at least 12 months were recruited at Imperial College Healthcare NHS Trust hospitals.

The researchers found that the compound MLE4901 significantly reduced the average total number of flashes during the four-week treatment period, as well as their severity, compared to when the patients received the placebo for four weeks. It also helped to reduce the impact of flashes on the women’s lives, improving sleep.

Dr Julia Prague, first author of the study, commented: “Despite the fact that for millions of women their menopausal symptoms are intolerable so many are suffering in silence because it is a taboo subject and treatment options are limited. It was so exciting to see the lives of those who participated in the study become transformed when their flushes improved once taking the new drug. They could sleep through the night, and be less embarrassed in the daytime; they told me they felt ‘human again’.”

Professor Dhillo added: “These are exciting findings which could be practice-changing. The plan now is to find out if the NK3R blocker, MLE4901, can be as safe and effective over a long term period in a larger group of patients.”